O-nitrobenzyl liposomes with dual-responsive release capabilities for drug delivery

Abstract

To improve the therapeutic efficacy of anticancer drugs and reduce its toxic side effects, we synthesized a series of amphiphilic o-nitrobenzyl molecules 4-(4-N,N,N,N-dicarboxymethyl-diethylenetriamino)acetoxymethyl-3-nitro-N,N-dialk-ylbenzamide (N,N-NB-DTPA) with good photolysis property and acid sensitivity. Simultaneously, N, N-NB-DTPA liposomes composed of the o-nitrobenzyl molecules have good biocompatibility, low hemolysis rate and cytotoxicity, and the drug encapsulation efficiency of the liposomes exceeds 70%. N, N-NB-DTPA-DOX liposomes possess good stability and can keep uniform distribution in PBS solution for 10 days. The drug release rate of these drug-loaded liposomes reaches to the maximums under pH 5.0 and 30 min UV irradiation, revealing pH/UV dual-responsiveness of these drug-loaded liposomes. The low pH makes DOX separate from these drug-loaded liposomes, and the UV irradiation leads to o-nitrobenzyl ester bond cleave, which contribute to accelerate the release of drug from drug-loaded liposomes. Furthermore, N, N-NB-DTPA-DOX liposomes after UV irradiation have better therapeutic effect than single DOX·HCl, which may result from the production of nitrosobenzaldehyde derivatives after UV irradiation.